Summary of Work: Associations have been reported between polymorphisms in the D4 dopamine receptor (D4DR) gene and the serotonin transporter linked-promoter region (5-HTTLPR) to the human temperament dimensions of Novelty Seeking and Harm Avoidance, respectively. Although consistent with Cloninger's hypothesized psychobiological model of temperament and character, many studies failed to replicate these findings. This study tested whether the psychobiological model taps the genetic architecture of personality by exploring associations between these candidate genes and the dimensions of the Temperament and Character Inventory (TCI) and by examining its phenotypic structure. Of the 946 male and female participants in the Baltimore Longitudinal Study of Aging who were administered the TCI, 587 were genotyped for a 48 base-pair repeat polymorphism in the D4DR gene and 425 were genotyped for a 44 base-pair insertion or deletion in the 5-HTTLPR gene. There was no significant association between polymorphisms in the D4DR gene and Novelty Seeking. There was also no association between polymorphisms in the 5-HTTLPR gene and Harm Avoidance. The factor structure of the TCI did not reveal the hypothesized phenotypic structure. This investigation found no support for the temperament-character model at either the biological or psychological level.